Intricate organic molecules, such as synthetic and natural bioactive molecules, typically include a hydrocarbon skeleton containing a large number of aliphatic C—H bonds. Oxidized functionalities containing oxygen and/or nitrogen typically decorate the hydrocarbon skeleton. The identity and position of the oxidized functionalities within a molecule are believed to strongly affect the biological activity of the molecule. Thus, reactions that selectively introduce an oxidized functionality into an organic framework are of particular significance in the synthesis of bioactive molecules.
A few general reaction classes have emerged for introducing oxidized functionality into organic frameworks. These reaction classes include functional group interconversions, C—C bond forming reactions of pre-oxidized fragments, and olefin oxidations. Using these reactions, modern synthetic planning is often focused on the use and maintenance of oxidized functionalities once they have been introduced into the molecule.
In contrast, iron enzymes routinely perform catalytic, selective oxidations of isolated sp3-hybridized C—H bonds in intricate molecules. Examples of these enzymes include cytochrome P-450 and methane monooxygenase (MMO). The selective reactivity of these natural catalysts is dependent on elaborate protein binding pockets. Although these binding pockets provide enzymes with good specificity and reactivity, they also limit the general applicability of the enzymes in the oxidation of a broad range of substrate molecules.
The paradoxical challenge in developing a useful oxidation reaction for intricate molecules is to provide a composition, such as a reagent and/or a catalyst, that is both highly reactive and predictably selective for oxidation of inert and ubiquitous C—H bonds. Moreover, to be useful in intricate molecule synthesis, the reaction preferably has a reactivity and a selectivity that are general for a broad range of substrates. Such a reaction could streamline complicated syntheses by providing a general way to install oxidized functionalities at a late-stage, thereby reducing unproductive chemical manipulations associated with carrying them throughout a synthetic procedure.